A Metabolism-Based Test to Diagnose Autism Spectrum Disorder and its Subtypes in Early Childhood

 描述（由申请人提供）：自闭症谱系障碍（ASD）现在被诊断为68名儿童中的1名，最近的报告引用了美国50名儿童中的1名。平均诊断年龄超过4岁。需要一种可靠的基于生物标志物的测试来早期诊断幼儿ASD，以改善认知，社会功能和沟通等结果。这将减少家庭和社会的经济和情感负担。2012年，Stemina开始了一项自筹资金的I期等效研究，研究对象是近400名ASD、发育迟缓（DD）和典型发育（TD）儿童的血浆样本。从这些研究中，我们开发了基于ASD和TD儿童代谢生物标志物差异的计算模型，可以区分ASD和TD患者，准确率约为80%。 Stemina寻求资金，以招募1500名患者参加一项明确的临床研究，以开发一种基于生物标志物的诊断测试，能够以超过80%的准确率对ASD相对于其他发育迟缓进行分类。此外，我们建议确定ASD谱中存在的可用于个性化治疗的代谢亚型。该研究将包括18至48个月的ASD、DD和TD儿童。从市售诊断检测的角度来看，纳入DD患者是本拟定研究的一个新颖且重要的方面。我们的最终目标是：（1）能够早期诊断和治疗;（2）阐明ASD患者亚型的代谢差异，以从个体生物化学角度适当匹配每个患者的最佳可用治疗;以及（3）确定整个谱中患者的生物化学改变，这将为新疗法提供靶点。我们将采用我们在第一阶段开发的创新代谢组学方法，包括将正交色谱分离方法与非靶向和靶向高分辨率质谱法相结合。我们的研究目标是确认在I期研究中发现的生物标志物，扩展代谢亚型的生物标志物谱，并通过创建更好地描述这种异质性综合征的生物标志物亚型组来优化ASD测试的准确性。基于我们的I期数据，我们相信这项临床研究也将使我们能够确认ASD亚型的特定代谢生物标志物。这种表征ASD的创新方法将允许医生根据患者的个体代谢提出最合适的治疗建议。

 DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) is now diagnosed in 1 of 68 children with recent reports citing as many as 1 in 50 children in the United States. The average age of diagnosis is more than 4 years. There is a need for a reliable biomarker-based test for earlier diagnosis of ASD in young children to improve outcomes such as cognition, social function and communication. This will subsequently decrease the financial and emotional burden on families and society. In 2012, Stemina began a self-funded Phase I equivalent study of plasma samples from nearly 400 ASD, Developmental Delay (DD) and Typically Developing (TD) children. From these studies, we developed computational models based on metabolic biomarker differences in ASD and TD children that could differentiate ASD from TD patients with an accuracy of about 80%. Stemina seeks funding to enroll 1500 patients in a well-defined clinical study to develop a biomarker-based diagnostic test capable of classifying ASD relative to other developmental delays at greater than 80% accuracy. In addition, we propose to identify metabolic subtypes present within the ASD spectrum that can be used for personalized treatment. The study will include ASD, DD and TD children between 18 and 48 months of age. Inclusion of DD patients is a novel and important aspect of this proposed study from the perspective of a commercially available diagnostic test. Our ultimate goals are to: (1) enable early diagnosis and treatment; (2) elucidate metabolic differences in subtypes of ASD patients to properly match the best available treatments for each patient from an individual biochemical perspective; and (3) identify biochemical alterations in patients across the spectrum that will provide targets for novel therapies. We will employ the innovative metabolomics approaches that we developed in Phase I, including coupling orthogonal chromatographic separation methodologies with both non- targeted and targeted high resolution mass spectrometry. Our study objectives will be to confirm biomarkers that were discovered in Phase I, expand those biomarker profiles for metabolic subtypes, and optimize the ASD test accuracy by creating panels of biomarker subtypes that will better describe this heterogeneous syndrome. Based on our Phase I data, we believe this clinical study will also allow us to confirm specific metabolic biomarkers of subtypes of ASD. This innovative approach to characterizing ASD will allow physicians to suggest the most appropriate treatment based on the individual metabolism of the patient.